A critical component of lupus treatment is monitoring for early detection of disease flares/manifestations and comorbidities. Metabolic syndrome, a condition that predisposes to atherosclerotic disease, could have an important influence on the morbidity and mortality of patients with SLE and should be routinely examined in lupus patients. Now, we have determined the factors associated with metabolic syndrome in a sample of SLE patients from Puerto Rico and found that older age, low socioeconomic status, lack of exercise, thrombocytopenia, increased ESR, higher disease activity, and the use of prednisone > 10 mg/day were independently associated with metabolic syndrome.
We found a higher prevalence of metabolic syndrome in patients with SLE (38.2%) compared with previous studies.24,25
For example, Chung, et al.
found a prevalence of 32.4% using the World Health Organization definition and 29.4% using the NCEP/ATP III classification criteria.24
Furthermore, El Magadmi, et al
showed a prevalence of 18% using the latter classification.25
These differences could be attributed in part to the classification criteria we used (AHA/NHLBI), which is more inclusive than the previous ones: including a lower fasting blood glucose threshold (≥ 100 mg/dL) and disease-specific pharmacologic treatments for the definition of its different components.1
The association of demographic–socioeconomic factors (older age and low socioeconomic status) with metabolic syndrome is consistent with the previous reports.4,5,26–29
In the general population, metabolic syndrome is more prevalent in older individuals.4,5,26–28
Anther important finding of the present study is that patients with metabolic syndrome were more likely to have the government health insurance of Puerto Rico. In Puerto Rico, patients receive their medical care through either the government health system (a managed care system for the medically indigent population) or the private healthcare industry (based on a fee-for-service system). The eligibility for the government health insurance is determined by the annual family income adjusted for the number of individuals in the household. For example, a family of four members with a combined annual income of 8220 US dollars or less is eligible. According to US standards, this income is below poverty level. In agreement with our findings, some studies have reported that a low household income increases the risk of metabolic syndrome.28,29
Furthermore, several studies have shown that a lower socioeconomic level is related to higher morbidity and mortality in patients with SLE.30–32
Taken together, these findings stress the need for early intervention in vulnerable groups to improve the course and outcome of chronic diseases, including SLE.
The association of metabolic syndrome with thrombocytopenia, higher ESR, and disease activity is noteworthy. However, whether lupus activity is a factor in the development of metabolic syndrome or whether metabolic syndrome is contributing to disease activity is unclear. It is well known that metabolic syndrome confers a pro-inflammatory state characterized by increased circulating adipocytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), leptin, resistin, plasminogen activator inhibitor-1 (PAI-1), and acute-phase reactants such as C-reactive protein.2,3
However, patients with SLE have higher plasma leptin and TNF-α levels than healthy-controls.33
Furthermore, TNF-α and IL-6 are associated with increased body mass index, abnormal lipid profile, and disease activity in patients with SLE.34–38
Thus, adipocytokines could have an important role in the development of metabolic syndrome and its association with disease activity in lupus patients.
Patients with metabolic syndrome were more likely to use prednisone >10 mg/day during the disease course. This finding could be reflective of their higher disease activity. However, this association could also be related to the fact that glucocorticoids promote hypertriglyceridaemia, increased fatty acid flux to the liver, and insulin resistance throughout the development of visceral fat.39
Therefore, because of deleterious side effects of glucocorticoids, including the possible association with metabolic syndrome, drug therapy should be kept to the lowest effective dose and alternative treatments should be considered early during the course of disease.
Although metabolic syndrome is an important risk factor for coronary artery disease, only a marginal association with myocardial infarction was observed. Moreover, no association with angina pectoris or cerebrovascular accidents was detected. This is probably related to the low number of patients with SLE who had arterial events and the shorter disease duration of our study sample. Longitudinal studies with longer follow-ups would be required to clearly assess the impact of metabolic syndrome on the cardiovascular outcome of lupus patients.
Some differences are noted between our study and others examining metabolic syndrome in SLE. In contrast to the present study, El Magadmi. et al.
found that SLE women with metabolic syndrome were of the same age as those without metabolic syndrome.25
Moreover, El Magadmi, et al.
and Chung, et al.
did not find any association of metabolic syndrome with lupus disease activity or glucocorticoid use.24,25
These differences could be related to variability in the study sample (e.g., ethnicity), length of disease duration, and methodology to assess clinical and outcome variables.
The present study has some limitations. First, non-lupus control subjects were not included. However, the prevalence presented here seems to be slightly higher than that reported for Puerto Ricans.40
For example, using ATP III criteria, Gómez, et al.
found that 34.2% of Puerto Rican women have metabolic syndrome.40
Second, because this is a cross-sectional study, it is possible that some patients had metabolic syndrome before study visit. Finally, other factors known to be associated with metabolic syndrome, particularly pro-inflammatory cytokines or procoagulant factors such as TNF-α, IL-6. fibrinogen, and PAI-1, were not measured.2,3
The presence of these factors could have a role in the emergence of metabolic syndrome in lupus patients.
Despite these limitations, the results presented here have several clinical implications. Metabolic syndrome is an independent risk factor for atherosclerotic disease; thus, it is important to identify patients at risk to develop metabolic syndrome early in the course of SLE. The implementation of strategies such as using alternative immunomodulator/immunosuppressive therapy (other than prednisone) and programs aimed at weight reduction, nutritional counselling and exercise might decrease the risk of metabolic syndrome. However, prospective studies, including interventional trials, are needed to address the role of metabolic syndrome in the course and outcome of lupus.